PIPERLAB RESEARCH
Our Questions
We investigate the membrane trafficking events in the endocytic system that control the degradation of membrane proteins and the organization of membrane protein complexes
Ubiquitin-dependent Trafficking
When Ubiquitin is attached to membrane proteins, it can direct those substrates into different membrane trafficking pathways. In endosomes, Ubiquitin ushers proteins into intralumenal vesicles that are then delivered to the lysosome for degradation. We are studying how Ubiquitin works as this sorting signal and what endosomal proteins recognize Ubiquitin.
Ub-dependent Internalization
Ubiquitin works as an internalization signal to recruit proteins for clathrin-mediated endocytosis. We are interested in the structure and function of Ub-binding proteins that may mediate endocytosis of ubiquitinated membrane proteins
Protein Interactions
We adapted the yeast 2-hybrid assay to simultaneously uncover multiple transient protein interactions within a single screen by using a strategy termed DEEPN (dynamic enrichment for evaluation of protein networks). This approach incorporates high-throughput DNA sequencing and computation to follow competition among a plasmid population encoding interacting partners.
Myelin membrane protein complexes
Myelin, crafted by Schwann cells, relies on Myelin Protein Zero (MPZ) and Peripheral Myelin Protein 22 (PMP22) for integrity. MPZ stabilizes the sheath, aiding layer adhesion. PMP22 regulates sheath thickness. Mutations in either gene cause peripheral neuropathies, disrupting nerve function. Both proteins are vital for efficient nerve impulse transmission. But how these proteins work at the structural and cellular level remains to be clearly determined.
Alternative Fate of Ubiquitinated Membrane proteins
Different types of ubiquitin chains are decoded by different ubiquitin-binding machines. We found that different types of polyubiquitination on membrane proeins in the Golgi and endosomal compartments are substrates for a new cohort of ubiquitin-dependent proteases that cleave lumenal and cytosolic domains for proteasomal degradation.